Does Pro12Ala Polymorphism Enhance the Physiological Role of PPAR2?
Figure 2
Physiological and metabolic roles of PPAR. In adipose tissue PPAR is involved in lipid storage, which reduces circulating free fatty acids (FFA). In adipose tissue PPAR blocks the proinflammatory role of macrophages as well the secretion of resistin both by macrophages and adipocytes which favors the uptake and metabolism of glucose in the liver, muscle, and other peripherals organs. Adipose tissue also secretes adiponectin, which favors indirectly the activation of AMP kinase in the liver, heart, and muscle. AMPK phosphorylates a number of enzymes involved in fatty acid oxidation and glucose metabolism as well the synthesis and release of GLUT4. In the endothelial tissue, PPAR favors the cholesterol efflux and at the same time, as consequence of the lowering of inflammatory signals, the recruitment of macrophages, thus delaying the atherosclerosis. Overall, the outcome of downstream effectors results in the decrease of proinflammatory cytokines, free fatty acids, and plasma glucose by increasing its uptake resulting in the increase of generalized insulin sensitivity and reduction of lipid accumulation in the liver, cardiac and skeletal muscle, and arteries as well as the diminishing of chronic inflammation, prothrombotic state, and atherosclerosis.
